Hydralazine: mode of action at the neuroarterial junction.

1. Hydralazine relaxes the rat tail artery by a direct action on vascular smooth muscle cells, which appears to be modulated by the action of sympathetic nerve terminals. 2. There is a gradient of response to hydralazine in arteries from normotensive Wistar rats, the proximal segments being poorly responsive. This gradient disappears after denervation with 6-hydroxydopamine in vitro. 3. Exogenously added purines inhibit noncompetitively the vasodilator response to hydralazine in denervated segments from normotensive Wistar rats. Their order of potency is 2-Cl-adenosine > adenosine > ATP > inosine. 4. The effect of hydralazine in innervated, poorly responsive segments is greatly potentiated by theophylline (50 mumol/l) and propranolol (5 mumol/l). These results, together with the effect of denervation, suggest that there are endogenous purines leaking from the nerve terminals under our experimental conditions. 5. Hydralazine produces a marked inhibition of stimulus-induced contraction and 3H release after [3H]noradrenaline loading. The mechanism of this prejunctional action appears to be different from the mechanism of the postjunctional effect.